Studies of the interaction of hematopoietic cells and viruses have mainly concentrated on members of the Parvoviridae and with our interest in hepatitis-associated aplastic anemia, novel putative hepatitis agents. B19 parvovirus infects erythroid progenitor cells and infection in humans causes both the hematologic syndromes transient aplastic crisis and pure red cell aplasia as well as the common childhood exanthem fifth disease. Provoked by reports that B19 parvovirus might be involved in the etiology of rheumatoid arthritis, we have collaborated in studies using the polymerase chain reaction to analyze synovial tissues in patients with arthropathy: B19 DNA was detected in both rheumatoid and non-rheumatoid patients. As in our studies of B19 in hepatitis, these results suggest that the virus may persist in small amounts in tissues without medical consequence. Using a related simian Erythrovirus (SPV), may offer an animal model for human disease, and we have reproduced one of the medical consequences of B19 infection, hydrops fetalis, by experimental uterine inoculation during the mid-trimester of pregnancy. Other parvoviral studies include development of adeno-associated virus vectors based on other adeno-associated virus strains, and comparative studies of hemagglutination and tissue tropism of these viruses. In addition, we have pursued further studies to determine the early events of AAV infection, including the nature of the cell surface receptor for AAV-2.Our studies of putative novel hepatitis viruses have concentrated on the recently described family of putative circoviruses, collectively known as TTV. This virus was first identified in a patient with transfusion-associated hepatitis, but its role in human disease still remains unclear. We have developed new PCR primers to detect TTV, and with these assays we can detect TTV sequences in ~ 80% of American blood donors, but the high degree of sequence variation suggests that current assays may not detect all TTV strains. In our studies we can show that the virus is associated with B lymphocytes in the peripheral blood and bone marrow, and in addition we have a method for in vitro culture of the virus. Our culture studies confirm that this is a novel ~16 nm icosahedral virus, and suggest that the virus may need helper functions from other viruses for replication. Studies of the interaction of different TTV strains, with hematopoietic cells are continuing.